A major focus of the study during the past year has been to continue to better understand HIV-1 induced cell death and latency formation at the molecular and cellular levels and to test therapeutic interventions in animal models. The lab continued its ongoing studies of different factors to better understand T cell longevity during HIV infection. The results of these studies are designed to help uncover and define the mechanisms involved in CD4 T cell depletion by specific viral gene products and in the context of viral infection, as well as the processes that drive latent infection. It was found that viral DNA integration into the host chromosome triggers DNA-PK activation, leading to death of the majority of CD4 T cells infected with HIV-1. 1a. Defined a role for JAK-STAT signaling in latency maintenance in vitro; exploring FDA-approved JAK inhibitors to determine their role. 1b. Identification of VprBP as a regulator of HIV-1 latency. Mechanism is under investigation. 2a. Demonstrated productive, spreading infection in resting effector memory CD4s 2b. Studying co-receptor usage in resting CD4s as a model for CCR5-tropic HIV preference during transmission.